In osteoblasts, retinoic acid (RA) modulates the synthesis of various proteins, including collagen. However, little is known about the effects of RA on the regulation of interstitial collagenase synthesis and collagen degradation. After treatment of primary osteoblast-enriched (Ob) cells from fetal rat calvariae with 100 nM all-trans-RA (tRA), collagenase mRNA levels, as determined by Northern blotting, did not change after 2 h, increased by 13- to 18-fold after 6 h, and remained elevated until 48 h. Exposure of Ob cells to 10 nM to 1 microM tRA, 13-cis-RA, and 9-cis-RA induced collagenase mRNA in a dose-dependent manner. Collagenase mRNA induction by RA was blocked by cycloheximide. RA increased the stability of collagenase mRNA in Ob cells, suggesting posttranscriptional regulation. Exposure of Ob cells to RA induced immunoreactive procollagenase in medium, as determined by enzyme-linked immunosorbent assay and Western blotting. RA action on collagen degradation was examined in [3H]proline-pulsed intact calvariae chased with and without tRA for 72 h. The release of [3H]hydroxyproline into culture medium was increased by 64% in the presence of 10 nM to 1 microM tRA. In conclusion, RA increases collagenase synthesis and collagen degradation in bone and is likely to play an important role in bone remodeling.

The prevalence of obesity, a condition associated with increased health risks, has risen significantly over the past several decades. Although obesity develops from energy imbalance, its etiology involves a multitude of other factors. One of these factors are endocrine disruptors, or “obesogens”, when in reference to obesity. Bisphenol A (BPA), a known endocrine disruptor used in plastic materials, has recently been described as an environmental obesogen. Although BPA-free products are becoming more common now than in the past, concerns still remain about the obesogenic properties of the compounds that replace it, namely Bisphenol S (BPS), Bisphenol F (BPF), and Bisphenol AF (BPAF). The purpose of this review is to investigate the relationship between BPA substitutes and obesity. Literature on the relationship between BPA substitutes and obesity was identified through PubMed and Google Scholar, utilizing the search terms “BPA substitutes”, “bisphenol analogues”, “BPS”, “BPF”, “BPAF”, “obesity”, “obesogens”, “adipogenesis”, “PPARγ”, and “adipocyte differentiation”. Various population-based studies were assessed to gain a better understanding of the epidemiology, which revealed evidence that BPA substitutes may act as obesogens at the pathophysiological level. Additional studies were assessed to explore the potential mechanisms by which these compounds act as obesogens. For BPS, these mechanisms include Peroxisome proliferator-activated receptor gamma (PPARγ) activation, potentiation of high-fat diet induced weight-gain, and stimulation of adipocyte hypertrophy and adipose depot composition. For BPF and BPAF, the evidence is more inconclusive. Given the current understanding of these compounds, there is sufficient concern about exposures. Thus, further research needs to be conducted on the relationship of BPA substitutes to obesity to inform on the potential public health measures that can be implemented to minimize exposures.